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ARS Home » Pacific West Area » Pullman, Washington » Animal Disease Research Unit » Research » Publications at this Location » Publication #371349
Research Project: Genetic Impact and Improved Diagnostics for Sheep and Goat Transmissible Spongiform Encephalopathies

Location: Animal Disease Research Unit

Title: Caprine PRNP polymorphisms N146S and Q222K are associated with proteolytic cleavage of PrPC

Author
item MADSEN-BOUTERSE, SALLY - Washington State University
item STEWART, PAULA - Roslin Institute
item WILLIAMSON, HELEN - Roslin Institute
item Schneider, David
item GOLDMANN, WILFRED - Roslin Institute

Submitted to: Genetics Selection Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/9/2021
Publication Date: 6/19/2021
Citation: Madsen-Bouterse, S.A., Stewart, P., Williamson, H., Schneider, D.A., Goldmann, W. 2021. Caprine PRNP polymorphisms N146S and Q222K are associated with proteolytic cleavage of PrPC. Genetics Selection Evolution. 53. Article 52. https://doi.org/10.1186/s12711-021-00646-x.
DOI: https://doi.org/10.1186/s12711-021-00646-x

Interpretive Summary: Expression of the cellular prion protein (PrP-C) is crucial for the development of prion diseases, including scrapie in sheep and goats. Amino acid changes in PrP-C or a reduced amount of PrP-C can modulate susceptibility to infection. In sheep, prion protein genotypes (PRNP) associated with resistance to scrapie are also associated with the relative abundance of C1, a natural cleavage fragment of PrP-C. In goats, other PRNP genotypes associate with resistance to scrapie but their associations with PrP-C cleavage is unknown. This study compared the relative abundance of the C1 fragment in the brain of healthy goats bearing either wild type PRNP or polymorphisms (I142M, H143R, N146S, or Q222K). As compared with wild type PRNP, the relative abundance of the C1 fragment was significantly associated with the Q222K and N146S polymorphisms, both of which confer strong resistance to scrapie in goats. Thus, altered abundance of the C1 fragment is not unique to sheep nor exclusive to the Q171R polymorphism that is associated with strong resistance to scrapie in sheep.

Technical Abstract: Expression of the cellular prion protein (PrPC) is crucial for the development of prion diseases. Amino acid changes in PrPC or a reduced amount of PrPC may modulate disease resistance. The relative abundance of C1, a natural a-cleavage fragment of PrPC, was previously found to be associated with a resistant PRNP genotype in sheep. Goats are another small ruminant where classical scrapie susceptibility is under strong genetic control. In this study, we assessed PrPC in goats for the existence of similar associations between PrPC fragments and genotype. Brain tissue homogenates from scrapie-free goats with wild type PRNP or polymorphisms (I142M, H143R, N146S, or Q222K) were deglycosylated prior to immunoblot for assessment of the relative abundance of the C1 fragment of PrPC. The presence of K222 or S146 alleles demonstrated significantly different relative levels of C1 compared to that observed in wild type goats, which suggests that the genotype association with C1 is neither unique to sheep nor exclusive to the ovine Q171R dimorphism.